Alpha fetoprotein (AFP) is a glycoprotein which is produced in high amounts during pregnancy. Biochemically, AFP exhibits charge lectin microheterogeneity. Results from our laboratory have shown that the microheterogeneous nature of AFP changes markedly during normal development. However, it is currently not certain if these findings reflect a physiological change in AFP function or merely indicate an alteration in the biochemistry of this glycoprotein. AFP isolated from term core blood, although not mitogenic itself, can enhance the mitogenic activity of growth factors and may function to modulate cell proliferation during fetal development. No mitogenic activity was observed in midgestation amniotic fluid, which also contains increased levels of AFP. Thus, AFP proliferative activity may vary with fetal development. The relationship between developmental changes in AFP microheterogeneity and biological activity is of major interest. In the series of experiments proposed herein, we will attempt to characterize the developmental aspects of AFP microheterogeneity and biological activity. We will use the monkey as a model to carefully define these ontogenic changes and to compliment and extend data obtained from the use of human fetal material, which is obviously limited. The charge and lectin microheterogeneity of AFP will be evaluated in the species throughout gestation. Monkey fetal tissue will be removed at various stages of gestation to allow the characterization of the production of AFP by these tissues. Additionally, we will use both the monkey and the human to elucidate the relationships between charge and lectin microheterogeneity and the expression of AFP proliferative activity. Finally, the biochemical basis for AFP microheterogeneity and biological activity will be elucidated. The results of these studies will greatly add to our knowledge of the biochemical and physiological importance of AFP to normal fetal development.